Researchers have found new genetic clues in fragile X syndrome, which is the most common cause of inherited intellectual disability and seizures. This new study suggests that fragile X results from an inherited genetic error in a gene called FMR1 and the error prevents the manufacture of a protein called FMRP, which causes overactive transmitters that send out too much information.
Researchers at Washington University studied a case of fragile X syndrome and found that a FMR1 gene is completely disabled, eliminating the FMRP protein that regulates electrical signals in the brain and causing a host of behavioral, neurological and physical symptoms. The study subject had only a single error in this gene and exhibited only two classic traits of fragile X, allowing the researchers to parse out a previously unknown role for the gene.
Co-senior author Vitaly A. Klyachko said, "This individual case has allowed us to separate two independent functions of the fragile X protein in the brain and by finding the mutation, even in just one patient, and linking it to a partial set of traits, we have identified a distinct function that this gene is responsible for and that is likely impaired in all people with fragile X."
The finding raises the possibility that drugs recently tested as treatments for fragile X syndrome may be ineffective, at least in part, because they only dialed down the brain's receivers, presumably leaving transmitters on overdrive. The researchers said, "We can't rule out the possibility that additional problems also are caused by this mutation and are present in fragile X, but this research specifies at least one additional dysfunction not previously recognized."
The research has been published online in the Proceedings of the National Academy of Sciences (PNAS).